Bidentate Phosphine Research Articles

Palladium-Catalyzed C-N Coupling in the Synthesis of Benzodiazepines

Abstract: This review article is focused on the reactions, which include the syntheses of various classes of benzodiazepines in the presence of a Pd catalyst. The catalyst used here belongs to the transition metal group and nowadays, there is keen interest in numerous methods for the coupling reaction in the presence of a catalyst to prepare the biologically active heterocyclic compounds. In particular, the use of domino reactions as inter- or intramolecular processes is reported as an efficient and eco-compatible tool to obtain differently functionalized benzodiazepines. 2,3-benzodiazepines having pharmaceutical interest are synthesized via asymmetric catalysis. The catalyst used in this synthesis is palladium-chiral bidentate phosphine complex and thiazolium-derived carbine. The 1,3-benzodiazepines are prepared by A3 coupling. In this reaction, the propargylamine was first added to the isocyanates. After that, hydroxylation of alkyne occurs in the presence of a Pd catalyst in a one-pot manner to yield the 1,3-benzodiazepines.

Effect of ligand coordination on the mechanism and regioselectivity of cobalt-catalyzed hydroboration/cyclization of 1,6-enynes

The 3d transition metal-catalyzed cyclization of enynes provides a sustainable and useful strategy for the construction of cyclic compounds. Controlling the regioselectivity is a central challenge for the hydrofunctionalization of multiply unsaturated substrates such as 1,6-enynes. Herein, we report a computational mechanistic study of the cobalt-catalyzed hydroboration/cyclization of 1,6-enynes in the presence of three representative ligands including bidentate nitrogen ligand and phosphine ligand as well as tridentate nitrogen-based ligand. A detailed analysis is carried out on the ligand-substrate interactions to understand the effect of ligand coordination on the mechanism and regioselectivity. Our results indicate that although the initial catalyst-substrate complexes adopt the pseudo-trigonal bipyramidal geometries for the two nitrogen-based ligands, there is a remarkable difference in the free energy surfaces. The steric repulsions and hydrogen bonding interactions between the substrate and the ligand play important roles in regulating the competing migration insertion. Energy decomposition analyses are further performed for the subsequent σ-bond metathesis to illustrate the impacts of steric and electronic effects on the regioselectivity and the electrostatics and orbital interactions are disclosed to be the dominant factors. This work provides a deeper understanding of the specific structural and electronic properties of the cobalt complexes and their potential influences on the reactivity and selectivity.

Nickel(I)-Phenolate Complexes: The Key to Well-Defined Ni(I) Species.

Phosphine-stabilized monovalent nickel complexes play an important role in catalysis, either as catalytically active species or as decomposition products. Most routes to access these complexes are highly ligand specific or rely on strong reducing agents. Our group recently disclosed a path to access nickel(I)-phenolate complexes from bis(1,5-cyclooctadiene)nickel(0) (Ni(cod)2). Herein, we demonstrate this protocol's broad applicability by ligating a wide range of mono- and bidentate phosphine ligands. We further show the versatility of the phenolate fragment as a precursor to nickel(I)-alkyl or aryl species, which are relevant to Ni catalysis or synthetically useful nickel(I)-chloride and hydride complexes. We also demonstrate that the chloride complex can be synthesized in a one-pot procedure starting from Ni(cod)2 in good yield, making this protocol a valuable alternative to current procedures. Single-crystal X-ray diffraction, IR, and EPR (or NMR) spectroscopy were employed to characterize all of the synthesized nickel complexes.

Synthesis and Electrochemical Investigation of Phosphine Substituted Diiron Phosphadithiolate Complexes

AbstractThis work reports on ligand exchange reactions between a [FeFe] hydrogenase model containing the higher homologue (PhosDT) and phosphines selected to cover a variety of electronic properties and possible coordination modes. Additionally, the amount of the phosphines and the reaction temperature were varied to study the formation of complexes with multiple phosphines or altered binding modes. Due to steric effects caused by the position of the bridgehead, the phosphines bind preferentially at the more accessible iron centre on the phosphinate averted side. While all ligand exchanges resulted in a ligand‐specific main product at room temperature, reflux conditions induced decomposition in case of PhosDT‐(κ2‐dppe) and PhosDT‐(κ2‐dppv) and a change in the binding mode for the dppm containing complex. Moreover, we highlight two novel iron complexes obtained as side products of the reactions with dppe and dppv, while in case of dppm an additional model with two bridging phosphine ligands was generated. Finally, the six novel phosphine substituted PhosDT models were electrochemically investigated, revealing a cathodic shift compared to the starting material due to the increased electron density at the iron atoms. Moreover, the models with monodentate ligands exhibit a different CV pattern for the FeIFeI/FeIFe0 process than complexes with bidentate phosphines.

Phosphino-Phosphination Reactions: Frustrated Lewis Pair Reactivity of Phosphino-Phosphonium Cations with Alkynes.

The phosphino-phosphonium cations of the form [R3 PPR'2 ]+ are labile and provide access to the constituent Lewis acidic and Lewis basic fragments. This permits frustrated Lewis pair-type addition reactions to alkynes, affording unprecedented phosphino-phosphination reactions and giving cations of the form [cis-R3 PCHC(R'')PR'2 ]+ . This reactivity is further adapted to prepare several examples of a rare class of dissymmetric cis-olefin-linked bidentate phosphines.

Copper-Catalyzed Enantioselective and Regiodivergent Allylation of Ketones with Allenylsilanes.

We report herein a regiodivergent and enantioselective allyl addition to ketones with allenylsilanes through copper catalysis. With the combination of CuOAc, a Josiphos-type bidentate phosphine ligand and PhSiH3 , allyl addition to a variety of ketones furnishes branched products in excellent enantioselectivities. The regioselectivity is completely reversed by employing the P-stereogenic ligand BenzP*, affording the linear products with excellent enantioselectivities and good Z-selectivities. The linear Z-product could be converted to E-product via a catalytic geometric isomerization of the Z-alkene group. The silyl group in the products could provide a handle for downstream elaboration.

Copper‐Catalyzed Enantioselective and Regiodivergent Allylation of Ketones with Allenylsilanes

AbstractWe report herein a regiodivergent and enantioselective allyl addition to ketones with allenylsilanes through copper catalysis. With the combination of CuOAc, a Josiphos‐type bidentate phosphine ligand and PhSiH3, allyl addition to a variety of ketones furnishes branched products in excellent enantioselectivities. The regioselectivity is completely reversed by employing the P‐stereogenic ligand BenzP*, affording the linear products with excellent enantioselectivities and good Z‐selectivities. The linear Z‐product could be converted to E‐product via a catalytic geometric isomerization of the Z‐alkene group. The silyl group in the products could provide a handle for downstream elaboration.

Cerium(IV) Nitrate Complexes With Bidentate Phosphine Oxides

AbstractThe reactions between ceric ammonium nitrate, (NH4)2Ce(NO3)6, (CAN) and the bidentate phosphine oxides, 4,5‐bis(diphenylphosphine oxide)‐9,9‐dimethylxanthene (L1), oxydi‐2,1‐phenylene bis(diphenylphosphine dioxide) (L2), 1,2‐bis(diphenylphosphino)ethane dioxide (L3) and 1,4‐bis(diphenylphosphino)butane dioxide, L4 have been investigated. The crystal structures of the molecular Ce(NO3)4L1 (1), and ionic [Ce(NO3)3L32][NO3]⋅CHCl3 (3), [Ce(NO3)3L32][NO3] (4) and the polymeric [Ce(NO3)3L41.5] [NO3] (5) and the cerium(III) complex [Ce(NO3)2L12][NO3] (2) are reported. The thermal stability of the complexes has been examined by thermogravimetry with the gaseous decomposition products analysed by infrared spectroscopy. Evolution of CO2 is found for both Ce(III) and Ce(IV) complexes with the later also forming NO2. The formation of the complexes in solution has been studied by 31P NMR spectroscopy and further complexes [Ce(NO3)3L12]+[NO3]− and [Ce(NO3)2L13]2+2[NO3]− identified in CD3CN solution. The complex (1) exists as a single molecular species in solution and is stable in dichloromethane whilst (3) decomposes on standing in both CD2Cl2 and CD3CN to Ce(III) containing species. Complexes of L2 have been identified by solution 31P NMR spectroscopy and these decompose in solution to give Ce(NO3)3L22. This study represents the first structural characterisations of Ce(IV) complexes with bidentate phosphine oxides.

Phosphino‐phosphinations: Frustrated Lewis Pair Reactivity of phosphino‐phosphonium cations with alkynes

The phosphino‐phosphonium cations of the form [R3PPR’2]+ are labile and provide access to the constituent Lewis acidic and Lewis basic fragments. This permits frustrated Lewis pair‐type addition reactions to alkynes, affording unprecedented phosphino‐phosphination reactions and giving cations of the form [cis‐R3PCHC(R”)PR’2]+. This reactivity is further adapted to prepare several examples of a rare class of dissymmetric cis‐olefin‐linked bidentate phosphines.

Synthesis of New Chelating Phosphines Containing an Aryl Chloride Group

AbstractThe syntheses of bidentate and tripodal phosphine ligands containing aryl chlorides were achieved in 4 and 7 steps respectively, starting from diethyl malonate.

Palladium-Catalyzed Oxidative Amination of Unactivated Olefins with Primary Aliphatic Amines

Direct coupling of unactivated olefins with primary alkylamines is considered to be an efficient but unknown method for the construction of complex amines. Herein we report a catalytic intermolecular oxidative amination of unactivated olefins with primary aliphatic amines based on the combination of a palladium catalyst, a bidentate phosphine ligand, and duroquinone. A range of secondary allylic amines were obtained in good yields with excellent regio- and stereoselectivity. Mechanistic control experiments revealed that the reaction proceeds by allylic C(sp3)-H activation and nucleophilic amination. The utility of the protocol is further demonstrated with the late-stage modification and streamlined synthesis of drug molecules.

Reduction of Triphenylphosphine Oxide to Triphenylphosphine by Phosphonic Acid.

A novel method for the iodine-mediated reduction of phosphine oxides (sulfides) to phosphines using phosphonic acid under solvent-free conditions is described. By using a combination of H3PO3 and I2, both tertiary monophosphine oxides and bis-phosphine oxides were reduced under this system, readily producing monodentate and bidentate phosphines, respectively, in good yields. Notably, chiral (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl dioxide could be also tolerated without racemization. This new approach is inexpensive and features simple conditions and a wide substrate scope.

Mechanistic Insight into Palladium/Brønsted Acid Catalyzed Methoxycarbonylation and Hydromethoxylation of Internal Alkene: A Computational Study.

Density functional theory (DFT) calculations were performed to study the palladium/Brønsted acid-catalyzed methoxycarbonylation and hydromethoxylation reactions of internal alkene. The calculated results show that the pyridyl group (N atom) in bidentate phosphine ligand with built-in base (L1) plays a crucial role in controlling the selectivity. With the help of the pyridyl group, the methanolysis steps in the methoxycarbonylation reaction and the hydromethoxylation reaction become easy, and both the linear ester methyl 3,4-dimethylpentanoate (P1) and the hydromethoxylation product 2-methoxy-2,3-dimethylbutane (P2) could be obtained. In contrast, the possibility of leading to branched ester P1' was ruled out according to our calculations. The steric effect could account for the observed selectivity. In the presence of the DPEphos ligand (L2) that does not bear the pyridyl group, the methanolysis step in the methoxycarbonylation reaction becomes the rate-determining step with a high overall energy barrier. Neither linear nor branched methoxycarbonylation product could be generated. The palladium/Brønsted acid co-catalyzed hydromethoxylation also become difficult without the assistance of the pyridyl group in the presence of the L2 ligand. Instead, TsOH-catalyzed hydromethoxylation reaction could take place to generate the ether product P2.

Catalyst Comparison for Additive-Free Acceptorless Dehydro­genation of Indoline Derivatives

AbstractA group of thirteen catalysts of type [Ru(Cp/Cp*)(P–P)(MeCN)]PF6, bearing cooperative or noncooperative bidentate phosphine ligands, were evaluated for the catalytic acceptorless dehydrogenation of indoline. The systematic comparison revealed that the optimal cooperative catalyst structure included a Cp ancillary ligand, and an N,N-disubstituted P,P-disubstituted 1,5-diaza-3,7-diphosphacyclooctane ligand, denoted as (PR 2NR′ 2). A cooperative complex bearing a PPh 2NPh 2 ligand exhibited about a twofold longer lifetime than a noncooperative analogue with (diphenylphosphino)ethane (dppe) as the supporting bisphosphine ligand. The cooperative catalyst effectively dehydrogenated a range of indoline substrates to give substituted indoles.

Regioselective coupling of benzyl chlorides with allyl and allenyl boronates catalysed by a bidentate phosphine ligand/palladium catalyst.

A palladium-catalysed aromative benzylic allylation and allenylation of benzyl chlorides with allyl and allenyl pinacolborates is described for the first time. The reactions proceed smoothly in the presence of a bidentate phosphine ligand to afford normal cross-coupling products in good yields. This novel synthetic procedure exhibits good tolerance for various electron-withdrawing and -donating functional groups linked to aromatic rings and is also well tolerant of sensitive functional groups such as NO2, CF3, CN, and COOMe. The utilisation of a bidentate ligand and heating are essential to transformation. The DFT calculation results reveal that wide-bite-angle bidentate ligands are beneficial to the formation of an η1-benzyl-η1-allylpalladium intermediate and that the normal coupling is thermodynamically favourable.

Ni‐Ion‐Chelating Strategy for Mitigating the Deterioration of Li‐Ion Batteries with Nickel‐Rich Cathodes

Ni-rich cathodes are the most promising candidates for realizing high-energy-density Li-ion batteries. However, the high-valence Ni4+ ions formed in highly delithiated states are prone to reduction to lower valence states, such as Ni3+ and Ni2+ , which may cause lattice oxygen loss, cation mixing, and Ni ion dissolution. Further, LiPF6 , a key salt in commercialized electrolytes, undergoes hydrolysis to produce acidic compounds, which accelerate Ni-ion dissolution and the interfacial deterioration of the Ni-rich cathode. Dissolved Ni ions migrate and deposit on the surface of the graphite anode, causing continuous electrolyte decomposition and threatening battery safety by forming Li dendrites on the anode. Herein, 1,2-bis(diphenylphosphino)ethane (DPPE) chelates Ni ions dissolved from the Ni-rich cathode using bidentate phosphine moieties and alleviates LiPF6 hydrolysis via complexation with PF5 . Further, DPPE reduces the generation of corrosive HF and HPO2 F2 substantially compared to the amounts observed using trimethyl phosphite and tris(trimethylsilyl) phosphite, which are HF-scavenging additives. Li-ion cells with Ni-rich cathodes and graphite anodes containing DPPE exhibit remarkable discharge capacity retentions of 83.4%, with high Coulombic efficiencies of >99.99% after 300 cycles at 45°C. The results of this study will promote the development of electrolyte additives.

Synthesis of Novel Cavitand Host Molecules via Palladium-Catalyzed Aryloxy- and Azidocarbonylation

Novel, elongated, resorcine[4]arene-based cavitands were synthesized via various consecutive reaction steps, including homogeneous catalytic aryloxy- and azidocarbonylation processes. The effects of carbon monoxide pressure and temperature on the conversion were examined in aryloxycarbonylation. It was revealed that a reaction temperature of 100 °C is required to achieve complete conversion both with monodentate (PPh3) and bidentate (Xantphos) phosphines at different carbon monoxide pressures (1-40 bar). Using ten different phenols as O-nucleophiles, partial hydrolysis of the esters to the corresponding carboxylic acids took place-i.e., 58-90% chemoselectivities toward esters were obtained. Moreover, the influences of temperature, reaction time and the catalyst ratio on the selectivity and conversion were described in the case of azidocarbonylation reaction. The formation of the acyl azide with high chemoselevtivity can be achieved at room temperature only. The higher reaction temperatures (50 °C) and higher catalyst loadings favor the formation of the primary amide. The characterization of the target compounds (esters and acyl azides) was carried out by IR and 1H and 13C NMR. The discussion of the influences of various parameters is based on in situ NMR investigations.

Recyclable Palladium-Catalyzed Carbonylative Cyclization of Aryl Iodides and 2-Hydroxyacetophenones towards Flavones

AbstractA highly efficient heterogeneous palladium-catalyzed carbonylative cyclization of aryl iodides and 2-hydroxyacetophenones is developed. The reaction proceeds efficiently in DMSO at 120 °C under 3 bar of carbon monoxide by using 2 mol% of an MCM-41-immobilized bidentate phosphine palladium complex [MCM-41-2P-Pd(OAc)2] as the catalyst and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base, providing a general, efficient and practical approach for the assembly of a wide variety of flavones in mostly good to high yields from readily available starting materials. This supported palladium catalyst can be easily recovered via centrifugation of the reaction mixture and recycled more than nine times without any significant loss of its catalytic efficiency.

Stimuli-Induced Reversible Transformation between Decanuclear and Pentanuclear Gold(I) Sulfido Complexes.

Decanuclear and pentanuclear gold(I) sulfido complexes of phenanthrene- and dibenzothiophene-based diphosphine ligands were synthesized and characterized. Unprecedented stimuli-induced reversible transformation between decanuclear and pentanuclear gold(I) sulfido complexes was observed, which could be readily monitored by NMR and UV-vis absorption spectroscopy in solution. Remarkably, the decanuclear gold(I) sulfido complex (Au10-LPh) was found to show a highly reversible transformation process, which is stable for over 10 successive cycles in solution. The stimuli-induced reversible transformation behavior of the gold(I) sulfido complexes was found to depend on the P-P bite distance of the bidentate phosphine ligands.

Ag(I)/Lewis Acid Cooperatively Promoted Three-Component Coupling for Carbo-Heterofunctionalization of Alkenes

A silver oxidant/Lewis acid catalyst cooperatively promoted three-component carbo-heterofunctionalization of alkenes is reported. A broad range of nucleophiles, including H2O, alcohols, and anilines, can combine with a variety of 1,3-dicarbonyl compounds or analogues as radical precursors to realize difunctionalization of various styrene derivatives. Interestingly, mechanistic investigations demonstrate that the Ag(I) complex of bidentate phosphine ligand quickly oxidizes the radical intermediate generated from the addition of initial radical across alkene double bonds to form carbocation intermediates, which may be the reason behind the excellent yields and high selectivity of such reactions.